Canine Nonischemic Left Ventricular Dysfunction: A Model of Chronic Human Cardiomyopathy

• Published in: Journal of cardiac failure 2005-10, Vol.11 (8), p.638-644
• Main Authors: Nishijima, Yoshinori, Feldman, David S., Bonagura, John D., Ozkanlar, Yunusemre, Jenkins, Paula J., Lacombe, Veronique A., Abraham, William T., Hamlin, Robert L., Carnes, Cynthia A.
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers - blood; C-Reactive Protein - metabolism; Cardiomyopathies - physiopathology; Chronic Disease; Disease Models, Animal; Dogs; Dyssynchrony; Echocardiography, Doppler; Electrocardiography; Heart Conduction System - physiopathology; Heart Rate; Humans; Hypertrophy, Left Ventricular - physiopathology; Male; Models, Cardiovascular; Natriuretic Peptide, Brain - blood; Research Design; Stroke Volume; tachypacing; Time Factors; Troponin C - blood; Troponin I - blood; ventricular conduction delay; Ventricular Dysfunction, Left - blood; Ventricular Dysfunction, Left - physiopathology; Ventricular Remodeling
• ISSN: 1071-9164; 1532-8414
• DOI: 10.1016/j.cardfail.2005.05.006

The mechanisms of cardiac remodeling during chronic heart failure remain poorly defined. We sought to advance a chronic canine model of nonischemic cardiomyopathy. Male dogs (n = 6) received decremental right ventricular apical tachypacing (12 months) to achieve and maintain stable left ventricular (LV) dysfunction. After 10 months of tachypacing, 120 beats/min was sufficient to maintain stable LV dysfunction. Electrocardiography, echocardiography, and tissue Doppler imaging were done to evaluate electrophysiology, LV dimensions and function, and dyssynchrony during normal sinus rhythm. The 6-minute walk test was used to evaluate functional capacity. We observed increases in both QRS duration ( P < .0001) and QRS amplitude ( P < .0001). LV fractional shortening was reduced from a baseline of 38.0 ± 1.4% to 11.2 ± 1.4% ( P < .0001). LV end-diastolic dimension increased from 3.8 ± 0.1 cm at baseline to 5.3 ± 0.3 cm ( P < .0001); LV end-systolic dimension increased from 2.3 ± 0.1 cm to 4.7 ± 0.2 cm ( P < .0001). LV mass increased from 85.9 ± 3.5 g at baseline to 179 ± 13.7 g ( P < .0001). There was evidence of LV dyssynchrony ( P < .04) during both normal sinus rhythm and right ventricular tachypacing, compared with control dogs. The distance a dog walked in 6 minutes was significantly less at 12 months compared with normal controls (540 ± 32 m versus 277 ± 64 m, P < .008). This nonischemic model of canine cardiomyopathy reproduces many aspects of chronic human heart failure including reduced fractional shortening, dilated ventricular dimensions, increased LV mass, decreased functional capacity, and dyssynchrony.